| Summary: | <i>Campylobacter</i> is a leading cause of foodborne gastroenteritis. Recent studies have indicated a rise in fluoroquinolone-resistant (FQ-R) <i>Campylobacter</i> in cattle, where FQ is used to control bovine respiratory disease (BRD). To assess the effect of danofloxacin treatment on the development of FQ-resistance in <i>C. jejuni</i>, 30 commercial calves were divided into Group 1, Group 2, and Group 3 (<i>n</i> = 10), and were all inoculated orally with FQ-susceptible (FQ-S) <i>C. jejuni</i>; seven days later, Group 3 was challenged with transtracheal <i>Mannheimia haemolytica</i>, and one week later, Group 2 and Group 3 were injected subcutaneously with danofloxacin. Rectal feces were collected to determine relative percentages of FQ-R <i>Campylobacter</i> via culture. Before oral inoculation with <i>C. jejuni</i>, 87% of calves were naturally colonized by FQ-R <i>C. jejuni</i>. Two days after the inoculation, FQ-R <i>C. jejuni</i> decreased substantially in the majority of calves. Within 24 h of danofloxacin injection, almost all <i>C. jejuni</i> populations shifted to an FQ-R phenotype in both FQ-treated groups, which was only transitory, as FQ-S strains became predominant during later periods. Genotyping indicated that the spike seen in FQ-R <i>C. jejuni</i> populations following the injection was due mainly to enrichment of preexisting FQ-R <i>C. jejuni</i>, rather than development of de novo FQ resistance in susceptible strains. These results provide important insights into the dynamic changes of FQ-resistant <i>Campylobacter</i> in cattle in response to FQ treatment.
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